Cancer's sweet tooth becomes a target

A drug that blocks the way cancer cells generate energy could lead to a new class of cancer treatments.

The first human trial of the drug, published this week, is reported to have extended the lives of four people with an aggressive form of brain cancer.

The result is preliminary, but it suggests that, as an approach, tackling "cancer metabolism" is sound. "We are still a long way from a treatment, but this opens the window on drugs that target cancer metabolism," says Evangelos Michelakis of the University of Alberta in Edmonton, Canada, who led the trial.

Elsewhere, researchers have started experimenting with a host of other molecules that might target cancer metabolism. "It's about identifying which target is best," says Lewis Cantley of Harvard Medical School in Boston, Massachusetts, whose company Agios Pharmaceuticals is screening for such targets.

Most of these efforts stem from an observation dating back to the 1930s - that cancer cells generate energy via glycolysis. This is different to the way cells normally make energy, through aerobic respiration in specialised chambers called mitochondria. Ordinary cells do use glycolysis but only if they are short of oxygen, as it is hugely inefficient, gobbling up large amounts of glucose for very little energy (see diagram).

At the time, it was assumed that the switch to glycolysis was a product of the cell becoming cancerous, rather than the other way around. "It was seen as a follower, not a leader or driver," says Ronald Evans of the Salk Institute in La Jolla, California.

However, in 2008, Cantley showed that glycolysis may actually benefit cancer cells. Though it is inefficient in terms of energy, the process also generates the chemical building blocks for making cells, including amino acids for making proteins, fats for cell membranes and nucleotides to build a genome. As cancer cells replicate very rapidly, the finding suggests that glycolysis might actually help drive cancer.

A year earlier, Michelakis had shown that mitochondria could be "reawakened" in human cancer cells cultured in the lab, and in rats, by a drug called dichloroacetate (DCA). This suggested that mitochondria are not impaired in cancer, just underactive, and that switching cells back to using them might fight cancer.